PROTECTION BY HYPOXIC PRECONDITIONING AGAINST HYPOXIA-REOXYGENATION INJURY IN GUINEA-PIG PAPILLARY-MUSCLES

Objective: Developed tension in guinea-pig papillary muscles is depres sed by prolonged hypoxia; subsequent reoxygenation leads to a partial recovery that stabilizes after an early period of arrhythmia. We have investigated whether hypoxic preconditioning in these muscles (1) impr oves the recovery of developed tension, (2) protects against reoxygena tion arrhythmia, and (3) causes other significant electromechanical ch anges. Methods: Papillary muscles stimulated at 1 Hz were superfused w ith oxygenated Krebs solution for 60 min and either preconditioned (5 min of 3 Hz pacing under substrate-free hypoxic conditions, 10 min of normoxic recovery) or equilibrated for an extra 15 min. Muscles were s ubsequently challenged with substrate-free hypoxia (1 Hz), and reoxyge nated (1 Hz) for 60 min. Contractile performance, action potential par ameters, and indicators of arrhythmic activity were measured in 10 pre conditioned and 10 non-preconditioned muscles. Results: Developed tens ion in preconditioned muscles declined to the same level (10-15% contr ol) as in non-preconditioned muscles after 60 min hypoxia. A notable d ifference was that developed tension in the preconditioned muscles fai led to rebound during mid-hypoxia, a hallmark feature in non-precondit ioned muscles. The action potential duration and overshoot collapsed a t a significantly faster rate in hypoxic preconditioned muscles. Actio n potential recovery during reoxygenation was similar in the two group s of muscles, but recovery of developed tension was significantly stro nger in preconditioned (76.7 +/- 5.4%) than in non-preconditioned (42. 9 +/- 1.7%) muscles (P < 0.001). Reoxygenation provoked arrhythmic act ivity in all muscles, but the summed average duration was shorter (5.5 +/- 1.0 vs. 9.4 +/- 1.5 min) (P < 0.05) in the preconditioned muscles . Conclusions: Hypoxic preconditioning can significantly enhance post- hypoxia recovery of developed tension, and significantly attenuate arr hythmic activity, in guinea-pig papillary muscles. (C) 1997 Elsevier S cience B.V.